This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a ongoing project in collaboration with Howard Robinson. Our earlier work has shown a unique movement of active site zinc during the catalytic cycle. We are now exploring the structure-activity relationships in the formaldehyde dehydrogenase (FDH) active site. Using high throughput screening, we have identified novel compounds that inhibit FDH. The goal of the structural studies is to identify the interactions of the identified compounds in FDH site and use the information in designing better inhibitors of FDH that can be used for exporing the role of FDH in cellular metabolism